Abstract:
Staphylococcus aureus (S. aureus) is a major pathogen and New Zealand has higher rates of infection than other developed nations. Due to its ability to develop resistance to beta-lactam antibiotics, new forms of treatment are needed as S. aureus in both community and hospital setting have developed resistance to treatment. S. aureus also has developed the ability to evade the immune system, making effective treatments difficult to produce. The aim of this research is to test the feasibility of a vaccine using Staphylococcal enterotoxin-like toxin X (SElX) to fight against S. aureus infection. SElX was selected because 95% of human and animal S. aureus strains produce this novel superantigen, it is encoded in the genome and has previously been shown to be associated with disease severity. Secondly, assessment of the role of SElX in functional and binding studies along with murine infection models where S. aureus wild type and selx gene knock out strains infected into murine models were conducted. Experiments conducted showed that SElX and SElXT130A were successfully purified. An effective ELISA assay was developed and showed that the anti-SElX IgG antibodies raised in mice had a good response to SElX. However, the presence of anti-SElX IgG antibodies did not reduce the bacterial load of S. aureus used for infection after vaccination. Further investigation revealed that while the antibodies produced showed minimal inhibitory effects, increasing the concentration in assays had a profound decrease in inhibitory effects. Analysis of SElX in functional and binding studies showed that there were minimal proliferative properties and had weak binding to cell surface markers present on murine immune cells. The results from this study has shown that SElX produces good anti-SElX IgG responses in murine models but only has minimal inhibitory activities. While more research will need to be done on SElX (and other virulence factors) in different animal models that are representative to what is seen in humans, a vaccination that is cheap, effective and confers immunity in both community and the hospital setting might be produced.